Monoubiquitination of Histone H2B Blocks Eviction of Histone Variant H2A.Z from Inducible Enhancers

• DOI: 10.1016/j.molcel.2016.08.034
• Publication Date: 2016-10-01T17:47:34Z
• Authors: Gregory Segala; Marcela A. Bennesch; Deo Prakash Pandey; Nicolas Hulo; Didier Picard
• Keywords: info:eu-repo/classification/ddc/570; Transcriptional Activation; 0301 basic medicine; Gene Expression Profiling; Ubiquitin-Protein Ligases; DNA Helicases; Estrogen Receptor alpha; Ubiquitination; Epithelial Cells; Chromatin Assembly and Disassembly; Chromatin; DNA-Binding Proteins; Histones; 03 medical and health sciences; Enhancer Elements, Genetic; HEK293 Cells; Genes, Reporter; ddc:570; Cell Line, Tumor; ATPases Associated with Diverse Cellular Activities; Humans; Luciferases; Signal Transduction

Covalent modifications of histones play a crucial role in the regulation of gene expression. Histone H2B monoubiquitination has mainly been described as a regulator of transcription elongation, but its role in transcription initiation is poorly documented. We investigated the role of this histone mark (H2Bub1) on different inducible enhancers, in particular those regulated by estrogen receptor α, by loss- and gain-of-function experiments with the specific E3-ubiquitin ligase complex of H2B: RNF20/RNF40. RNF20/RNF40 overexpression causes repression of the induced activity of these enhancers. Genome-wide profiles show that H2Bub1 levels are negatively correlated with the accessibility of enhancers to transcriptional activators. We found that the chromatin association of histone variant H2A.Z, which is evicted from enhancers for transcriptional activation, is stabilized by H2Bub1 by impairing access of the chromatin remodeler INO80. We propose that H2Bub1 acts as a gatekeeper of H2A.Z eviction and activation of inducible enhancers.